A phase I trial of irinotecan administered as a 1 hour intravenous infusion, daily x 5, every 21 days was conducted in pediatric patients with refractory cancer. Twenty-one patients (15 male), median age 10 (range, 2-20) have received 48 courses (range, 0-15) of irinotecan. All patients were premedicated with ondansetron and dexamethasone. The starting dose was 30 mg/m[2] with escalation to 39 mg/m[2] and 50 mg/m[2] in subsequent cohorts. At the 50 mg/m[2] dose level, dose limiting myelosuppression occurred in 2/5 patients [1 heavily pretreated and 1 less heavily pretreated (</= 2 prior chemotherapy regimens, no prior bone marrow transplantation or central axis rediation, no bone marrow involvement)]. Other non-dose-limiting toxicities include: "early" diarrhea (n=1), "late" diarrhea (n=14), nausea (n=4), emesis (n=6), anxiety (n=1), peripheral sensory neuropathy (n=1), transient elevations of serum transaminases (n=4), constipation (n=3), and infection (n=4). Further accrual at the 50mg/m[2] dose level has been limited to less heavily pretreated patients. The maximum tolerated dose of irinotecan in both heavily and less heavily pretreated children with refractory cancer is higher than in adult patients treated on the same dosing schedule.